A very large number of diterpenoids possessing a labdane skeleton (FIG. 1) occur in nature (Connoly, J. D.; Hill, R. A Dictionary of Terpenoids, Chapman and Hall: London 1991). The interest in studying labdanes is heightened due to the wide range of biological activities of these compounds (Singh, M.; Pal, M.; Sharma, R. P. Plants Med., 1999, 65, 2-8.). They comprise a decalin system and a C-6 ring, which may be open or closed with an oxygen atom, as in manoyl oxide and its derivatives. Labdanes have been isolated from several plant families, such as Asteraceae, Labiateae, Cistacease, Pinaceae, Cupressaceae, Taxodiaceae, Acanthaceae, Annonaceae, Caprifoliaceae, Solanaceae, Apocynaceae, Verbenaceae and Zingiberaceae. In addition they have been isolated from marine algae of the genus Laurence, from Taonia atomaria and from the red alga Chondria tenuissima.
The conifers are an important source of diterpenoids. Several labdanes have been detected in the neutral fraction of the oleoresin of Araucaria excelsa, including manool as well as nor-labdanes (Caputo, R.; Mangoni, L.; Monaco, P. Phytochemistry, 1972, 11, 839-840). A variety of biological activities have been associated with labdane diterpenes including antibacterial, antifungal, antiprotozoal, enzyme induction, anti-inflammatory modulation of immune cell functions, as well as cytotoxic and cytostatic effects against human leukemic cell lines. (k. Dimas et al. Planta Med. 1998, 208-211; K. Dimas et al. Leukemia Res. 1999, 4065-4072). In addition to the (antimicrobial, enzyme and endocrine related) properties mentioned above, it is interesting that many labdane type diterpenes also exhibit significant properties against cancer cells. A number of labdane type diterpenes tested exhibited remarkable antiproliferative and cytotoxic activities (Itokawa, H. et all. Planta Med. 1988, 311-315; K. Dimas et al. Planta Med. 1998, 208-211; K. Dimas et al. Leukemia Res. 1999, 217-234; K. Dimas et al. Anticancer Res. 1999, 4065-4072).
Labdane furanoids, and forscolin derivatives are the subject of several patents and applications, including European Patent Application 93103605.7; International Patent Publication No. WO 97/45099; International Patent Publication No. WO 91/02525; and International Patent Publication No. WO 85/03637.
Liposomes, or phospholipid vesicles, are self-assembled colloidal particles that occur naturally and can be prepared artificially (Lasic, D. D. Liposomes: from Physics to Applications. Elsevier), as shown by Bangham and his students in the mid-1960s (Bangham, A. D. ed. (1983) Liposomes Letters, Academic Press). At first, they were used to study biological membranes; several practical applications, most notably in drug delivery, emerged in the 1970s. Today, they are a very useful model, reagent and tool in various scientific disciplines, including mathematics and theoretical physics, biophysics, chemistry, colloid science, biochemistry and biology. Liposomes were introduced as drug-delivery delivery vehicles in the 1970s. Early results were, however, rather disappointing, owing mainly to their colloidal and biological instability, and their inefficient and unstable encapsulation of drug molecules. Their utility was improved following basic research that increased our understanding of their stability and interaction characteristics.
In the scientific literature, there is reference to a great number of liposomic pharmaceutical forms. Many of these are in the clinical study stage and some other have been already registered and marketed. Among the medicines formulated in liposomic form, are econazole, amfotericin B, minoxidyl and some anticancer and antiviral medicines, which are in the clinical study stage.